Antinuclear antibody (ANA) specificity is of increasing importance in assisting identification of various autoimmune rheumatic disease syndromes. Further, the etiologies of the autoimmune diseases systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjogren's syndrome (SS), polymyositis (PM) and polymyositis-scleroderma overlap syndrome are unknown. Isolation, purification, and biochemical and immunological characterization of the autoantigens associated with these diseases are important steps which should: 1) contribute to our understanding of pathogenic mechanisms operative in these diseases; 2) help elucidate heterogeneous patient immune responses which may be valuable for diagnosis, classification and prognosis; and 3) result in the production of assays useful as tools for further research, and for treatment. The development of SLE-like disease models in murine strains such as NZB/NZW, BXSB, MRL, and Palmerston North has assisted investigation of these antigen-antibody systems, and correlation between clinical, serological and pathological findings. This proposal is the continuation of what has been highly successful, coordinated effort of associated investigators, using a multifaceted approach, to elucidate the role of nuclear acidic protein antigen (NAPA) systems in several rheumatic diseases. This approach includes purification, biochemical characterization, and determination of the inter-relationships of nuclear acidic protein antigens, including RNP, Sm, PM-1, SS-A, SS-B, MA, and Su. Affinity chromatography, "Western blot" technology, high performance liquid chromatography, amino acid and nucleic acid sequencing techniques, and a library of monoclonal antibodies will be employed. Investigation of the genetic, immunological, and hormonal regulation of nuclear acidic protein antigens and antibodies will utilize our developing knowledge of the cellular, serologic and histopathologic aberrations of the autoimmunity in the MRL mouse system. Determination of the basic functions and biological importance of nuclear acidic protein antigens will be accomplished using the frog oocyte in vivo, and the rabbit reticulocyte in vitro for RNA transcription and protein translation systems.